This grant covers the investigation of a variety of subjects in three laboratories. The Arthritis Research Unit, the Development Biology Laboratory and the Laboratory for Carbohydrate Research, each under the supervision of one of the three principal investigators. These studies cover a range of biological and biochemical problems relating to the structure and function of mesenchymal tissues as well as related subjects. They include studies of the course and therapy of patients with various forms of bone and joint disease characterization of collagen metabolic products in patients with bone and joint diseases; studies of collagen biosynthesis in human cultured cells, especially in heritable disorders of connective tissue as well as study of collagen and elastin in adult disorders; characterization of degradative enzymes in tissues from patients with rheumatic diseases; characterization of cultured cells from inflammatory arthritis; study of mediators of inflammation in bone and joint disease such as prostaglandins and a variety of growth factors; studies of immunologic mechanisms in tissue injury; studies of lymphocyte physiology as relates to tissue injury; studies of enzyme catalysis; amino acid sequence analysis of collagen polypeptide chains, molecular and supramolecular organization of collagen fibrils; mechanisms of fibrillogenesis in vitro and in vivo; control of collagen type in embryonic development and related cell cultures, and in specific genetic abnormalities in mice and men; the control of collagenolytic enzyme systems in certain amphibian and mammalian tissues and in fibrotic states; and investigations on the detailed chemical structure of glycoproteins from a variety of sources.